[unreadable] The primary goal of this proposal is to organize a laboratory that can study complex neurobiological problems at levels ranging from the molecular to the behavioral and help translate those finding to clinically relevant treatments for smoking cessation. This Career Development Award would free up time to learn about clinical and translational research and develop collaborations with clinical researchers. The studies proposed therefore involve traditional pharmacological, biochemical, and behavioral experiments, as well as use of transgenic and knock-out technology but will be based on ongoing collaborations with clinical faculty. The career development plan involves attendance at seminars addressing translational research and hands on work with faculty members whose expertise is in human studies of smoking and smoking cessation. Finally, this proposal will allow time for attendance at meetings on transdisciplinary research on tobacco abuse, as well as the time to assist with experiments in laboratories focusing on clinical issues related to smoking cessation. The Specific Aims of this project are to provide a basic science background for the behavioral, neurochemical and molecular events underlying nicotine addiction and to design these studies so that findings can be translated into human studies and ultimately into new therapeutics for smoking cessation. These Aims will be achieved using wild-type mice, traditional knock-out mice that lack expression of the beta 2 subunit of the neuronal nicotinic receptor throughout development in all tissues, and mice that conditionally express this subunit only in particular brain areas under the control of the tetracycline-regulated promoter. Together these different approaches will build a bridge between molecular biological data on nicotinic receptor subtypes, the large body of behavioral pharmacological literature on the actions of nicotine in vivo, and human studies on the physiological and behavioral effects of smoking. [unreadable] [unreadable] [unreadable] [unreadable]